Collagen Type II–Derived Telopeptides Cause Tissue Damage in Human Cartilage Cultures Established From Total Arthroplasty

Objective To determine whether telopeptides of collagen type II could induce osteoarthritic tissue damage via receptor for the native protein by using human articular cartilage. Methods Cartilage slices were harvested from patients receiving total arthroplasty. Cartilage tissue cultures or primary chondrocyte cultures were treated with 30 µM N- or C-telopeptide (NT or CT) for 7 days or for 24 h. Loss of proteoglycan (PG) from cartilage was evaluated with 1,9-dimethylmethylene blue (DMMB) assay. Conditioned media or cell lysates were measured for levels of matrix metalloproteinases (MMPs), MMP-3 and MMP-13, or integrin beta-1 (ITGB1) with Western blotting or real-time polymerase chain reaction (PCR). Results Either NT or CT could induce significant loss of PG from cartilage than did phosphate-buffered saline (PBS), the delivery vehicle (18.45 ± 6.58 or 15.50 ± 4.91 µg PG/mg wet cartilage treated by NT or CT vs. 25.61 ± 4.14 µg PG/mg wet cartilage treated by PBS; P = 0.037 for NT, P = 0.004 for CT). Upregulation of MMP-3 and MMP-13 was induced by either NT or CT at 24 h (chondrocyte cultures) or Days 4 and 7 post-treatment (cartilage cultures). CT-induced stronger expression of ITGB1 in chondrocytes than did NT. Conclusion Telopeptides of collagen type II could damage human articular cartilage and upregulate MMP-3 and MMP-13. The catabolic effect of CT might be mediated by ITGB1.